Methyl triazines



United States Patent METHYL TRIAZINES Christoph J. Grundmaun and Ehrenfried Kober, Colum bus, Ohio, assignors to Olin Mathieson Chemical Corporation, a corporation of Virginia No Drawing. Application August 1,1956 Serial No. 601,363

7 Claims. (Cl. 260-249.9)

)ur invention relates to novel methyl triazines' useful as intermediates, allergenics, vesicahts and anesthetics and a method for their preparation. They have the formulae Rr-CHZ wherein R is hydrogen, a halogen, a hydroxy grou analkyl group, an aryl group, an alkoxy group, an aryloxy group, a thioalkyl group, a thioaryl group, an amino group, a monoalkylamino group, a monoarylamino group, a dialkylamino group, a diarylamino group or an aziridino group; R is a halogen, a hydroxy group, an alkoxy group, an aryloxy group, a thioalkyl group, a thioaryl group, an amino group, a monoalkylamino group, a monoarylamino group, a dialkylamino group, a diarylamino group, an aziridino group, or a R CHZ group; R is hydrogen, an alkyl group, an aryl group, a carbalkoxy group, or an aliphatic alkyl group substituted by 6m 6 N N Il Rz wherein R and R have the meanings described above, and Z is halogen, hydroxy or the residue of an organic or inorganic acid, i. e. the remainder of the acid after an H is removed. The alkyl and aryl groups contain not more than 8 carbon atoms. The useful alkyl groups in the various substituents include, for example, methyl, ethyl, propyl, butyl, amyl, hexyl, heptyl and octyl. The useful aryl groups include, for example, phenyl, tolyl and xylyl. Useful halogens include chlorine, bromine and iodine.

We have found that the compounds of our invention (except the compounds in which R or R is a hydroxy group) can be efficiently prepared by reacting a diazomethyl triazine of the following formula (in which R R and R have the meanings described above except that neither R nor R is a hydroxy group, the

group of R is a 'ice group.) with an inorganic or organic acid, viz:

Rr-CN': Bis-CHZ N N N H 6 HZ II Suitable organic acids include the aliphatic acids of 2 to 18 carbon atoms or more, such as acetic acid, propionic acid, acrylic acid, capronic acid, stearic acid, also aromatic acids, such as benzoic acid, phthalic acid, and heterocyclic acids, such as isonicot'inic acid, nicotinic acid, thiazoleL-Z-carbonic acid etc. The organic acids can be substituted withsubstituents which do not interfere with the reaction or with the other substituents R R and R at the molecule. Such substituents include in the case of aliphatic acids, for example, alkoxy and amino groups, and halogens. In the case 'of aromatic acids the same substituent and also nitro groups can be present.

The reaction of the substituted diazomethyl-s-triazines with the acids can be carried out under Widely different conditions according to physical and chemical properties of the employed acid. For instance, the acid can be used in the gaseous state and under anhydrous conditions, for instance, when working with the hydrogen halides. In other cases a more or less diluted aqueous solution of the acid can be employed, as it is for instance preferable, when working with sulfuric or nitric acid. In other circumstances the application of the liquid undiluted acid ispreferable, for instance, when working with the lower fatty acids. Solid acids, like benzoic acid can be re acted with the substituted diazomethyl-s-triazine in the melt. In any case the use of a suitable inert solvent is possible and often preferable to avoid undesirable side reactions.

With strong inorganic acids the reaction proceeds generallyin cold, sometimes dilution and cooling is necessary to keep the reaction under control. With the weaker 'or-= ganic acids it is often necessary in order to complete the reaction within a reasonable time to heat to temperatures below the decomposition temperature of the applied substituted diazomethyl-s-triazine, in general below 160 C, The preferred range of temperature in these cases is between 60 and C. The reaction proceeds with a stoichiometrical amount of the acid HZ, but an excess of the acid is in general not deleterious except in those cases, where it may cause undesired reactions with the other substituents R R and R The formed substituted methyl-s-triazines are generally easily isolated no by-products except nitrogen are formed.

A hydroxyl group of the triazine nucleus is sufiiciently acidic to destroy the diazo group; therefore the above method cannot be used to prepare, for example, 2-chloromethyl-4- and/or 6-hydroxy-l,3,5-triazines. This compound can be readily prepared, however, by treating the novel 2-halomethyl-4- and/or 6-halo-1,3,5-triazines with an alkali, e. g., dilute sodium carbonate or hydroxide. By the term alkali we mean the alkali metal hydroxides and carbonates. Under mild reaction conditions, the relatively stable halomethyl group. is substantially unafiected and the hydroxy compound is readily obtained.

The alkoxy and aryloxy compounds can also be prepared in better yields by the following method:

Rs-(ii N:

The reaction with hydrogen halide is carried out dry in an inert solvent. The second reaction can be accomplished by treating an alcohol solution of 2-halomethyl- 4,6-dihalo-l,3,5-triazine with a solution of an alkali metal, e. g., sodium, in an alcohol, e. g., methanol. Also, the hydroxy compounds can be produced by using diluted NaOH, or sodium carbonate, in the second reaction under mild reaction conditions so as not to affect the X group in the 2-position.

The diazomethyl compounds from which the novel compounds of this invention are prepared are described and claimed in our copending application Serial No. 601,343, filed August 1, 1956. They are obtained by reacting halogeno-l,3,5-triazines containing at least two halogen atoms directly connected with the triazine nucleus with diazo compounds which have at least one hydrogen atom available at the carbon atom which bears the diazo group. The reaction is expressed by the following general equation, wherein R and R have the meanings described above for the diazomethyl triazines and X is a halogen:

Using an excess of the diazo compound, i. e. at least 2 moles of dlaao compound per mole of triazine, under suitable conditions, the second halogen atom can react These bis-diazo-substituted triazines are generally unstable and therefore difficult to obtain in pure form.

The useful halogeno-1,3,5-triazines include, for example the known cyanuric trihalides, especially cyanuric chloride. Other suitable starting materials are Z-methyl- 4, G-dichloro-1,3,5-triazine, 2-phenyl-4,6-dichloro-1,3,5- triazine, 2,4-dichloro-1,3,5-triazine, and 2-amino-4,6-dichloro-l,3,5-triazine, 1

The useful diazo compounds are those which have at least one hydrogen atom available at the carbon atom which bears the diazo group. Thus, lower aliphatic diazo compounds, e. g., diazomethane, diazoethane, diazopropane, in general are suitable. Also bifunctional aliphatic diazo compounds like 1,6-diazo-hexane can be used. Diazoaralkyl compounds such as diazotoluene are useful. Diazocarbalkoxy compounds such as diazoacetic acid ester, e. g., methyl or ethyl diazoacetate, are useful. The reaction to produce the diazomethyl compounds is usually carried out in homogeneous phase in a solvent inert both to the-halotriazine and thedia zocompound. Such solvents are, for example, organic liquids such as ethers, e. g., diethylether and dioxane; aliphatic hydrocarbons, e. g., pentane, hexane, heptane; and aromatic and hydroaromatic hydrocarbons, e. g., benzene, toluene or the xylenes, tetralin and decalin. Y I The reaction is carried out by simply admixing the reactants. In many cases the reaction occurs spontaneously at room temperature or even below, when mixing the components dissolved in a suitable solvent. Sometimes it is preferable to heat the reaction mixture to a temperature below the spontaneous decomposition temperature of the diazo compound. In general, the upper limit of heating is around to C., while the preferred range of heating is between 0 and 80 C. If the diazo compound should be too volatile at elevated temperature, elevated pressure can be used. 1

The reactants are preferably used in stoichiometric proportions depending on the product desired, i. e., one mole of diazo compound per mole of triazine to form the monodiazotriazine or two moles of diazo compound per mole of triazine to form the bisdiazotriazine, although more or less can be used. As shown by the general equations above during the reaction one or two moles of the corresponding hydrohalogen acid will be generated. Usually these acids will be destroyed by' an excess of the diazo compound used according to the known reaction:

If it is desired to avoid any loss of the diazo compound by this side reaction, a strong tertiary organic base can be added to the reaction mixture to bind the formed hydrohalogen acid as a salt. Suitable bases for this purpose, are, e. g., triethylamine and tributylamine.

The diazomethyl compounds in which R is other than a halogen or a group, i. e. compounds in which R and/or R are alkoxy, aryloxy, thioalkyl, thioaryl, amino, monoalkylamino, monoarylamino, dialkylamino, diarylamino or aziridino, can be prepared by reacting compounds in which R and/or R are halogen with alkali metal alkoxides, alkali phenolates, alkali mercaptides, alkali-thiophenolates, ammonia, primary and/or secondary alkyl or aryl amines. For example, 2-diazomethyl-4,6-dihalo-1,3,5- triazine can be reacted with a metal alcoholate as by the following equation;

The reaction with the alkali metal alcoholate, for example, sodium methylate or ethylate, is accomplished by slowly adding an alcoholic solution of the triazine to an alcoholic solution of the alkali metal. The particular alcohol used as the solvent is of course that which corresponds to the alcoholate desired as a reactant. The reaction mixture should then stand for about one day at room temperature, after which a short (one-half to one hour) refluxing period is advar rt ageous,' The reaction mixture is then filtered .to remove the salt .and the 2-.diazomethyl-4,6-dialkoxy or diary1oxy-1,3,5-.triazine is .recovered by distilling off the remaining alcohol. rRurifica tion :of the product can be accomplished by extraction with a suitable solvent, such as the Skellysolves, .a group of solvents consisting of hexanes, .heptanes, octanes and solvent naphthas. The crystals obtained can thenbe sublimed in vacuo.

The preparation of -the .diazo compounds useful .in preparing the-compounds of our .invention will be .illustrated by reference to the following examples:

EXAMPLE 'I 2-diaz0methyl-4,6-dichlore-1,3,5-tfiia2ine 44.3 grams of cyanuric :chloride was dissolved in 800 ml. of ether. The :solution was slowly added at C. .upon stirring-to a solution of 0.5-0.6 mole (approximatev:ly 23 grams) ofdiazomethane dissolved .in 1000 .ml. of ether. The .same effect will be obtained if the diazomethane solution is added to the cyanuric chloride solution under the above conditions. The reaction mixture was allowed :to stand for about two :days at room temperature and then filtered to remove small amounts of solid by-products. The ether was removed from the filtrate by distillation, at room temperature, under a slight vacuum. The resulting residue was extracted three times with 800, Y500 and finally 300 ml. of hot Skellysolve C. After maintaining the extracts at a temperature of -'25' C. for 2 days, yellow starlets crystallized in a yield of 39.7.grams or 87.5% P. 110-111 C. This product is sufficiently pure for most purposes. For final purification these crystals were :sub'limed, preferably in small portions under atmospheric pressure at 100-125 C. yielding faint yellow long thin needles which melted at 111.5-

l.l2.5 C.

Percent Percent Percent Percent LG N 01 Calculated for 'C HN G1; F d

'EXA-MPLE II 2,4-bis-diaz0methyl-6-chlor0-1 ,3;5-triazine Cyanuric chloride, 14.6 grams, was dissolved .in 5.00 ml. of dry ether. The solution was slowly added -with stirring to'a solution of 23 grams-of diazomethane in 1000 ml. of ether 'kept at'O" C.

The reaction mixture was 'allowed to stand for seven days at room temperature and then filtered to remove small amounts of solid by-products. The :ether was removed from the filtrate, at room temperature by applying a slight vacuum. The resulting crystal slurry was extracted once withhot SkellysolveB. After. the extract was allowed to stand for four days at 25 C., 0.8 gram of yellow crystals precipitated. After recrystallization from Skellysolve C, the crystals decomposed in an interval from 92-120 C. These crystals are a mixture of approximately 50% of the mono-diazo compound "('I) of Example I and 50% of the bis-diazo compound (It) which can be separated by fractional crystallization from ether at 'low temperatures, if desired. However, this operation is connected with a considerable loss of material owing to its instability and reactivity.

6 EXAMPLE 1H .2-diaz0methy l-4-methyl-6-chl0r0-I,3j5-triazine The amount of 24.6 grams of 2-methyl-4,6-dichloro- 1,3,5-triazine was dissolved in 700 ml. of dry ether and slowly added upon stirring to the solution of 14 grams of diazomethane in 600 ml. of dry ether at -0 C. The reaction mixture was allowed to stand for about two days at room temperature and then filtered to remove small amounts of solid by-products. The ether and excess diazomethane were removed from the filtrate by distillation and the resulting residue extracted with "500 ml. Skellysolve C. ,After standing for several days at -f'25 C., a small amount of a yellow crystalline by-product precipitated and was removed by filtration. The filtrate was concentrated to about 200 ml. by vacuum distillation between 40 and 60 :C. Upon standing :at -125 9 0., yellow needles and ;yellow starlets :precipit'at'ed and were filtered off. The yellow needles and yellow :starlets were separated by hand. The needles .(0.8 gram) were recrystallized from Skellysolve C, yielding 0.24gram of very thin yellow needles which melted at 89-90 C.

Z-a'iazomethyl-4-phenyl-6-chl0r0-1,3,5-triazine The amount of 11.3 grams of 2-phenyl-4,6-dichloro- 1,3,5-triazine was dissolved in 700 ml. of ether and slowly added with stirring .to the solution of 025-03 mole (approximately 11.5 grams) diazomethane. The tempera.- ture was kept at 0C. The reaction mixture was allowed to stand for about seven days at room temperature and then filtered to remove small amounts of by-products. The ether and the excess diazomethane were removed from the filtrate by vacuum distillation at .room temperature. The resulting residue was extracted three times with Skellysolve C. Upon standing at 25 :C., 8.85 grams or 76.3% of yellow starlets precipitated which .had a melting point of 105-107" C. For fina'l purification the crystals were recrystallized once more from .Skellysolve C, M. P. 107-109 C.

' Percent Percent Percent Percent G N Cl Calcd. for CwHsN5Cl 61 30. 24 Foun EXAMPLE V 2-diaz0ethyl-4,6-dichl0r0:1.,3,5-triazine The amount of 18.45 grams A mol) cyanuric chloride dissolved in 350 ml. ether was added upon stirring to the solution of 0.3 mol diazoethane in 900 ml. .ether at 0 C. The reaction mixture was allowed :to warm up to room temperature and to stand for 15 hours. After filtration the ether was removed in vacuo and the oily residue was extracted two times with 750 ml..and 500 ml. of boiling Skellysolve C. After standing for one :day .at 20 C., a yellow .oil containing some crystals had separated from the Skellysolve extracts. The oil was separated by decantation and the Skellysolve extract evapo rated in vacuo to a small volume. 2.45 grams of 2-diazoethyl-4,6-dichloro-1,3,5-triazine crystallized in orange ;col

ored needles, melting at 97.5- C. after drying the latter small volume on a porous clay plate. From the aforementioned oil a "further crop of 1.1 grams of 2- diazoethyl-4,6-dichloro 1,-3,S-triazine was .obtained by extraction with Skellysolve C, followed by treatment of this extract as deseribedbefore. Thus the overall yield is 17.5%. The product can be recrystallized with Skellysolve C yielding yellow needles, -M. P. 100*101' IC.

Percent Percent Percent Percent C N C1 031011. for C5H3N5C1g 29. 43 1. 48 :FpIJJJld 29. 06 1. 73 35. 46

EXAMPLE VI 4,6-dichl0r0-1,3,5-triazinyl-2-diazqethyl-accrate Percent Percent Percent Percent C N 01 Calcd. I01. C7H5N5C1303 73 2;. 06 .53 2 .00 Fmmd 32. 32 1. 9s 26. 43 2e. 80

EXAMPLE VlI I Z-didzomethyl-4,6-dimethoxy-1,3,5-triazine The crude 2-diazomethyl4,6-dichloro-1,3,5-triazine, 38 grams, of Example I was dissolved in 650 milliliters of methanol. This solution was slowly added, with stirring and at 0 C., to a solution comprising 9.2 grams of sodium and 250 milliliters of methanol.

After standing for 24 hours the reaction mixture was refluxed for 30 minutes. The cooled reaction mixture was then filtered from the sodium chloride and the methanol removed from the filtrate by distillation. At the end of the distillation a slight vacuum was applied. The resulting residue was extracted six times with Skellysolve B. After cooling, 28.3 grams, or 78.4 percent of the theory, of yellow crystals of Z-diazomethyl-4,6-dimethoxy-1,3,5-triazine crystallized. The product was sublimed in vacuo (110 to- 135 C. bath temperature, 0.015 mm.) to giveyellow prisms which melted at 105 to 106 C.

2-diazomethyl-4,6-diethoxy-1,3,5-triazine When the same reaction as described in Example VII was carried out with ethanol instead of methanol, the 2-diazomethyl-4,6-dichloro-1,3,5-triazine was converted, with a yield of 70 percent of the theory, into 2-diazomethyl-4,6-diethoxy-1,3,5-triazine. The latter crystallized from ligroine in yellow prisms, melting at 62.5 C.

Percent Percent Percent Calculated for CgHnNsOz 45. 93 5.30 33.48 Found 46.07 5.30 33.30

EXAMPLE IX Z-diazomethyl-4,6-dithiomethyl-1,3,5-triazine 1.15 grams of sodium were dissolved in 50 grams of methanethiol, at a temperature between ---20 and 0 C.

The excess methanethiol' was 'allowed to evaporate at room temperature, and the solid residue suspended in 100 milliliters of xylene, cooled to 0 C., and 4.75 grams finely powdered 12-diazomethyl-4,6-dichloro-1,3,5-triazine added with stirring. The reaction was allowed to warm up to room temperature, stirred for 10 hours, and finally kept for 30 minutes between and C. All operations were carried out in an atmosphere of pure nitrogen. The reaction mixture was then filtered from insoluble material and the filtrate freed from xylene by vacuum distillation at 50 C. The residue was crystallized from Skellysolve C, yielding 3.75 grams percent of the theory) of 2-diazomethyl 4,6 dithiomethyl-1,3,5-triazine in the form of thin yellow needles. M. P. 112-115 C.

0 H g N s Oalulnted for COH'IN5S2 '33. 79 3.31 32.84 30. 07 Found 33. 54 3.10 33. 26 30.14

EXAMPLE X 2-diaz0methyl-4,6-dithi0ethyl-1,3,5-triazine Working as described in Example IX, 1.15 grams of sodium, 50 grams of ethanethiol and 4.75 grams of 2- diazomethyl-4,6-dichloro-1,3,5-triazine reacted to give 4.6 grams percent of the theory) of crude '2-diazomethyl-4,6-dithioethyl-1,3,5-triazine as an orange colored oil, solidifying at 0 C. The compound was purified by recrystallization from a low boiling petroleum ether forming yellow spheroidal crystals, melting at 34-35 C.

EXAMPLE XI Z-diazomethyl-4,6-dithiophenyl-1,3,5-triazine 1.15 grams of sodium were dissolved, under reflux in an atmosphere of nitrogen, with stirring in 85 grams of benzenethiol. The excess solvent was removed by vacuum distillation. After cooling, the solid residue was reacted, as described in Example IX, with 4.75 grams of 2- diazomethyl-4,6-dichloro-1,3,5-triazine, yielding 7.0 grams (83 percent of the theory) of crude 2-diazomethyl- 4,6-dithiophenyl-1,3,5-triazine. The compound was recrystallized from Skellysolve C, yielding 6.0 grams of yellow needles, melting at 98-99 C.

o H N s s 50.95 3.29 20.70 19.00 tzlsadffffif rfiii 56.8. 4.8 20.73 .9. .1

EXAMPLE XII Z-diazomethyl-4-amino-6-chlor0-1,3,5-triazine Ammonia was passed, for two hours, through a-reflux- O H N 01 Calculated for C4H O1N 28. 17 1. 75 49. 29 20. 79 Found 28. 54 1. 80 49. 19 20. 33

9 EXAMPLE XIII Z-diazomethyl-4,6-diamino-1,3,5-triazine A mixture of about 70 milliliters of liquid ammonia and 4.75 :grams of 2,4-dichloro-G-diazomethyl-1,3,5-triazine was kept at 60 C. for-eight hours in an autoclave. After the excess ammonia was allowed'to evaporate, the

reaction mixture was removed from the autoclave with ice cold concentrated ammonium hydroxide and filtered under vacuum, yielding 3.1 grams (82 percent) of crude 4,6 diamino 2 diazomethyl 1,3,5 triazine. The

.latter still contained a considerable amount of ammonium chloride, and so was digested several times with aqueous ammonium hydroxide, the resulitng paste being dried on a porous plate. To .remove the last traces of ammonium chloride, the 4,6-diamino-2-diazomethyl-1,3, 5-triazine was heated for about one minute with a mixture of 50 milliliters of ethyl alcohol, 25 milliliters of water, and 3 milliliters of concentrated ammonium hydroxide, and then filtered. The filter cake was extracted with ether and the remaining, slightly .colored :powder dried over potassium hydroxide. The '2-diazometh-yl-4, 6-diamino-1,3,5-triazine is practically insoluble in the usual solvents at temperatures which do not cause decomposition of the diazo group. Heated under usual conditions, 4,fi-diamino-Z-diazomethyl-1,3,5-triazine decomposes gradually above 230 C.

o H N Calculated for C4H5N 31. 79 3. 34 64. 87 Found 31. 82 4. 18 64. 1O

desired compound remained as a yellow oil in an 83 percent yield. It was purified by vacuum distillation and boiled at 1l0-115 C./.03S mm.

C s H Calculated for CuHnN 54. 74 '8. 04 Found" 54. 38 8.12

EXAMPLE .XV

Z-diazom ethyl-4-diethylamin0-6-chlor0-] ,3,5-triazine The reaction described in Example XIV was carried out with only 4 grams of diethylamine in an ethereal solution at room temperature. Working up after 24 hours resulted in 2-diazomethyl-4-diethylamino-6-chloro- 1,3,5-triazine in a yield of 79 percent of the theory. The product was obtained, after recrystallization from ethanol/water, in yellow prisms, melting at 52.5" C.

o H 01 V N Calculated for osnuonvt 42.39 4.89 15.64 37.08 Found 42. 23 4.93. 14.91 37.07

EXAMPLE XVI Z-dz'azomethyl-4,6-di-aziridino-1,3,5-triazine A solution of 5.4 grams of triethylamine and 5.0 grams of ethylene imine .in 100 milliliters of anhydrous ether Was slowly added at 0 C., withstirring, to asolution of Calculated for 0rH9N 47.528 4.47 ound- 47332 4.752

Examples of other materials useful for the preparation of the novel compounds of this application are 2-diazomethy1-4,'6-diphenoxy- 1 ,3,5-triazine 2-diazomethyl-4,6-bis-ethylamino- 1, 3.,5-triazine 2-diazomethyl-4,6-bis-phenylamino1 ,3,5-triazine 2-diazomethyl-4,6-bis-diphenylamino-l,3,5-triazine 2-diazotolyl-4,6-dichloro-1,3,5-triazine Lo-diazo [2(4,6-dichloro-1,3,51triazine) l-hexane.

Each of the above compounds can be prepare'c'l by first introducing the proper diazo group into the corresponding.2,4 dichloro -6 su bstituted 1,3,5 'tr'iazine. For example, reaction of diazomethane with 2,4-dichloro-6-phenoxy 1,3,5 triazine gives 2-diazornethyl-4 chloro-6-phenoxy-1,3,5-triazine. The chlorine in the 4- position is then replaced with the desired group. Reaction of sodium phenate with 2-diazo-methyl-4-chloro-6- phenoxy-l,3,5-triazine gives 2-diazomethyl-4,6-diphen oxy-l,3,5-triazine; reaction of 2-diazomethyl-4-chloro-6- ethylamino-1,3,5-triazine with ethylamine gives 2-diazomethyl-4,6-bis-ethylamino-1,3,5-triazine; reaction of 2-diazomethyl 4 chloro 6 phenylamino 1,3,5 triazine with aniline gives Z-diazomethyl 4,6 -'bi's-.pheny1 amino 1,3,5 triazine; reaction of .2 diazomethyl 4- chl'oro -6 diphenylamino 1,3,5 triazine with diphenylamine gives 2 diazomethyl 4,6 bis diphenylamino- 1,3,5 triazine. 2 diazotolyl 4,6 dichloro 1,3,5- triazine and 1,6 diazo [2(4,6 dichloro 1,3,5 tri' azine)]-hexane are prepared by reaction of cyanuric chloride with diazotoluene and 1,6-diazo-hexane respectively.

The compounds of our invention and their preparation will be further illustrated by the following examples:

EXAMPLE XVII Z-c'hl0r0methy'l-4,6-dichloro-1,3,5-triazine 30 grams of Z-diazomethyl-4,6-dichloro-1,3,5-triazine were dissolvedin .1500 milliliters of anhydrous ether and gaseous hydrogen chloride passed through the solution for 12 hours, finally with refluxing. 2.0 grams of insoluble'by products were filtered off and the ether removed by distillation. The residue was distilled in vacuo, yielding 25.38 grams (81 percent of the theory) of 2-chloromethyl-4,'6-dichloro-1,3,5-triazine, boiling point 69-71 C./0. 05 mm.; 11 1.5461. The substance is apparently dimorphous; two modifications melting at 20.5 C. and 36 C. were observed.

G .H Y .N Cl

Calculated for C HzCl3Na I24. 21 1.01 21.18 53.50 Found 24. 19 1. 29 p 21. 58 i 53. 08

Dry HCl was passed into a solution-comprising 20 grams of 2-diazomethyl-4,6-dimethoxy-1,3,5-triazine and 1300 milliliters of anhydrous ether for six hours. The reaction was started at C., and then allowed to come to room temperature. The reaction mixture was then refluxed for three hours while additional HCl was bubbled therein. The product was filtered yielding 17.8 grams of a yellowish solid. Upon removing the ether from the filtrate by distillation, 4.5 grams more of the solid yellowish product was obtained. The crude product thus obtained was treated with an ice-cold aqueous solution of sodium bicarbonate. The 2-chloromethyl-4,fi-dimethoxy- 1,3,5-triazine remained as a precipitate which was further purified by recrystallization from Skellysolve C. The yield was 4.8 grams, or 22.9 percent of the theory, of 2-chloromethyl-4,6-dimethoxy-1,3,5-triazine.

Per- Per- Per- Percent cent cent cent 0 H N 01 Calculated I01 CeHaNaOzCI 3,890 22 22. 15 18. 75 3 8 .35 22.11 18 58 Emma l 38.12 4.39 22. 18.48

EXAMPLE XIX 2-chloromethyl-4,6-dihydroxy-1,3,5-zriazine When the reaction described in Example XVIII was modified by extendingthe refluxing time to 48 hours, the precipitate consisted mainly of the hydrochloride of 2- chloromethyl-4,6-dihydroxy-1,3,5-triazine. (Found: N, 21.25 percent; Cl, 36.02 percent.) From the filtrate another crop of this compound was isolated, as described above, making a total yield of 82 percent, melting point 218-220 C. a I

o H 01 N Calcd. for C H ClgN3Oz 24. 24 2. 55 35.81 21. 23 Found 23. 97 3. 4s 35. 62 2o. 89

In this case a side reaction, consisting in the demethoxylation of the original 2-chloromethyl-4,6-dimethoxy-1,3,5- triazine, was caused by the prolonged action of the hydrogen chloride.

EXAMPLE XX 2-m0n0chloromethyl-4,6-dimethoxy-1,3,5-triazine 15.88 grams of 2-monochloromethyl-4,6-dichloro-1,3,5- triazine were dissolved in 600 milliliters of absolute methanol. To this there was added with stirring a solution comprising 3.68 grams of sodium and 250 milliliters of methanol, at 0 C. The reaction mixture was kept for five days at room temperature and finally refluxed for two hours. residue was extracted with 700 milliliters of hot Skellysolve C. The extract was kept overnight at -25 C. whereupon 12.5 grams or 82.5 percent of 2-monochlor0- methyl-4,6-dimethoxy-1,3,5-triazine melting point 5859 C., crystallized; Upon concentrating the Skellysolve C mother liquor to about 50 milliliters, 1.45 grams of product crystallized after one day at 25 C. This increased the total yield to 92.1 percent.

The methanol was removed under vacuum and the EXAMPLE XXI Z-hydroxymethyl-4,6-dimethoxy-I ,3,5-1riazine To an emulsion, of 9.1 grams X mole) off2-diazomethyl-4,6-dimethoxy-1,3,5-triazine in 50 milliliters water, 0.5 milliliter of concentrated sulfuric acid was added. The reaction mixture warmed up immediately and the diazomethyl compound was dissolved. After cooling, the solution was extracted with ether. The ether was removed, and 4.9 grams of a slightly yellow solid residue remained, melting point 108111 C., yield: 57 percent. The bydroxyrnethyl-triazine .can be recrystallized from Skellysolve C, yielding white needles, melting at 115-116 C.,

or it can be sublimated at 100 C. under normal pressure.

Calculated for otrnNaol 42.10 5.30 24.55 Found 41.99 v .5. 27 24.54

In this case the original sulfuric acid ester of 2-hydroxymethyl-4,6-dimethoxy-1,3,5-triazine was hydrolysed during the reaction.

EXAMPLE XXII Z-acetoxy-methyl-6,4-dimeth0xy-1 ,3,5-triazine 4.53 grams A mole) of 2-diazomethyl-4,6-dimethoxy- 1,3,5-triazine was added to 25 milliliters of acetic acid percent) and boiled for about three minutes. The

solution was poured into 800 milliliters of ice water, neutralized with sodium bicarbonate, and extracted with ether. Evaporationjofthe ether yielded 3.9 grams of a slightly yellow oil (yield: 74 percent of the theory), which was crystallized by cooling to about 20 C., and rewarming to room temperature. Long white needles were obtained on recrystallization from Skellysolve C, melting point 44.545.5 C.

o H N Calculated for osmlNlol 45.06 5.20 19.71 Found 44.99 5.26 v19.1

EXAMPLE XXIII Z-benzoyloxy-methyl-4,6-dimethaxy-1 ,3,5-tri azine o H N Calculated for C13H13N304 56.72 4. 76 .15. 27 Found 56. 86 4. 71 15.15

EXAMPLE XXIV 2+ [4 'amin0benz0yl0xy] -methyl-4,6-bis(diethylamino)- 1,3,5-triazine was removed in vacuo,, yielding 2.5 grams of an oil (yields 88.3 percent). When-theoil was dissolved in a small amount of acetic acid and water was added, white crystals precipitated upon standing at C. The precipitate was recrystallized from Skellysolve C, yielding small white spheroids, melting at 8889 C., of the compound named above, which has the following structure:

N% Him-Go o 0 0H5 N The compound possesses a mild but long lasting anesthetic action. I

o H N Calculated for omnmmm 61. 2 6 7. s 22. 57 Found 61. O8 7. 68 22. 58

Examples of other compounds of our invention are We claim:

1. The method of preparing methyl triazines which comprises admixing, at a temperature of about 0 C. to 160 C., an acid selected from the group consisting of strong inorganic mineral acids, acetic acid, benzoic acid and p-aminobenzoic acid, with a diazo triazine of the formula R1C\ /(II/R5 wherein R is selected from the group consisting of hydrogen, chlorine, alkyl, aryl, alkoxy, aryloxy, thioalkyl, thioaryl, amino, monoalkylamino, monoarylamino, dialkylamino, diarylamino and aziridino groups, R is selected from the group consisting of chlorine, alkoxy, aryloxy, thioalkyl, thioaryl, arnino, mo'noalkylamino,

monoarylamino, dialkylamino, diarylamino, aziridino and R3$Na groups wherein R has the meaning described below, R is selected from the group consisting of hydrogen, alkyl, aryl, and carbalkoxy groups and aliphatic alkyl groups substituted by wherein the alkyl group of the alkyl and alkyl-containing substituents of R R and R contains from 1 to 8 carbon atoms and the aryl group of the aryl and aryl-containing substituents of R R and R is selected from the group consisting of phenyl, tolyl and Xylyl.

2. The method of claim 1 in which the triazine is hydrolyzed to the corresponding carbinol.

3. The method of preparing 2-monochloromethyl-4,6- dimethoxy-1,3,5-triazine which comprises reacting hydrogen chloride with 2-diazomethyl-4,6-dimethoxy-1,3,5- triazine at a temperature of about 0 C. to 160 C.

4. The method of preparing 2-[4'-'amino-benzoyloxy]- methyl-4,6-bis(diethylamino)-1,3,5-triazine which comprises reacting p-aminobenzoic acid with 2-diazomethyl-4, 6-bis(diethylamino)-1,3,5-triazine at a temperature of about 0 C. to 160 C.

5. The method of preparing 2-acetoxymethyl-4,6-dimethoxy-1,3,5-triazine which comprises reacting acetic acid with 2-diazomethyl-4,6-dimethoxy-1,3,5-triazine at a temperature of about 0 C. to 160 C.

6. The method of'preparing 2-benzoyloxymethyl-4,6- dimethoxy-1,3,5-triazine which comprises reacting benzoic acid and 2-diazomethy1-4,6-dimethoxy-1,3,5-triazine at a temperature of about 0 C. to 160 C.

7. The method of preparing 2-chloromethyl-4,6-dichloro-1,3,S-triazine which comprises reacting hydrogen chloride with 2-diazomethyl-4,6-dichloro-1,3,5-triazine at a temperature of about 0 C. to 160 C.

Chemical Abstracts, vol. 47, page 4344 (1953 abstract of Ettel et al., Chem.. Listy, vol. 46, pages 289-92) (1952).

Beilstein, vol. 26, page 315, System No. 3942. 

1. THE METHOD OF PREPARING METHYL TRIAZINES WHICH COMPRISES ADMIXING, AT A TEMPERATURE OF ABOUT 0* C. TO 160* C., AN ACID SELECTED FROM THE GROUP CONSISTING OF STRONG INORGANIC MINERAL ACIDS, ACETIC ACID, BENZOIC ACID AND P-AMINOBENZOIC ACID, WITH A DIAZO TRIAZINE OF THE FORMULA
 4. THE METHOD OF PREPARING 2-(4''-AMINO-BENZOYLOXY)METHYL-4,6-BIS(DIETHYLAMINO)-1,3,5-TRIAZINE WHICH COMPRISES REACTING P-AMINOBENZOIC ACID WITH 2-DIAZOMETHYL-4 6-BIS(DIETHYLAMINO)-1,3,5-TRIAZINE AT A TEMPERATURE OF ABOUT 0* C. TO 160* C. 